Joseph D. Mocanu, Ph.D.
Laboratory of Dr. Fei-Fei Liu
Department of Medical Biophysics
University of Toronto
Canada

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Gene therapy can be defined as the insertion of new genetic programs, or the suppression of existing ones, in living organisms.  In normal tissue, this can entail the correction of a pre-existing defect or the enhancement of a deficiency. However, in cancer, it is primarily used to tilt the balance away from cell division towards cell death, or to stimulate a host immune response. Optical molecular imaging permits the direct visualization of these processes as they unfold, and allows for an improved understanding of the numerous parameters involved in designing gene therapy agents. The rapid characterization of their kinetics, biodistribution, and specificity can expedite development cycles and the eventual translation to the clinic.

Presented here are several examples of past and present work highlighting the potential synergy between cancer gene therapy and optical molecular imaging: i) the use of bioluminescence imaging (BLI) to characterize adenoviral vectors that preferentially express genes in Epstein-Barr virus-positive cancers, and the identification of compounds that change vector biodistribution; ii) combined fluorescence and bioluminescence imaging to establish a system to assess adenoviral biodistribution in metastatic models; iii) the use of automated tiling fluorescence microscopy to evaluate the microdistribution of new oncolytic viruses and antisense molecules in several human tumor models; and iv) the generation of models exploring radiotherapy-induced leukemia through the tracking of hematopoietic stem cell migration and proliferation in irradiated tissues via BLI.

These studies provide a platform to further explore and optimize future gene therapy strategies, and to branch out in new areas, such as regenerative medicine and stem cell biology; both avenues in which gene therapy has been showing renewed promise and interest.


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